Cancer, bacterial infections, fungal infections, and immune disorders continue to be a significant health problem despite the substantial research efforts and scientific advances reported in the literature. Some of the most frequently diagnosed cancers include prostate cancer, breast cancer, and lung cancer. Prostate cancer is the most common form of cancer in men. Breast cancer remains a leading cause of death in women. Lung cancer is a leading cause of cancer death worldwide, responsible for over one million deaths annually according to a study from year 2008. Lung cancer is often attributed to long-term exposure to tobacco smoke, but genetic factors and exposure to asbestos and air pollution have been reported as factors contributing to the development of lung cancer. Another cancer, melanoma, is a form of skin cancer in which over one-hundred thousand new cases are diagnosed each year in the United States according to the American Cancer Society. Current treatment options for these cancers are not effective for all patients and/or can have substantial adverse side effects. Another unmet need associated with cancer therapy is treatment of chronic infections in patients with a weakened immune system due to receiving radiation therapy, chemotherapy, and/or other anti-cancer therapies. Such chronic infections include bacterial, fungal, and viral infections.
In addition to the unmet needs in cancer therapy, various bacterial infections are becoming a more significant health concern due to the increase in bacterial infections resistant to current antibiotic therapies. One example is Staphylococcus aureus. It has been reported that multiple strains of Staphylococcus aureus have become resistant to multiple antibiotic medications commonly used to treat patients suffering from Staphylococcus aureus infections.
Another unmet medical need is for improved therapies to treat fungal infections. Fungal infections have been reported to afflict over one billion people each year, with infections by candida being one of the most common fungal infections in humans.
Adoptive cellular therapy has been investigated as a treatment option for patients suffering from cancer and other medical disorders. Restifo and coworkers recently reviewed progress in using adoptively transferred T cells to treat cancer. Restifo et al. in Nat. Rev. Immunol. (2012) vol. 12(4), pages 269-281. Recent efforts using adoptive cellular therapy to treat cancer build from earlier reports, such as U.S. Pat. Nos. 5,229,15 and 5,776,451, describing exposing lymphocyte cells to certain interleukins and then administering the resulting lymphocyte cells to a patient. More recent reports such as U.S. Pat. No. 7,998,736 and International Patent Application Publication No. WO 2012/129451 describe, for example, using T cells that have been modified to express certain proteins. Despite the research devoted to developing adoptive cellular therapy for treatment of medical disorders, improved methods and compositions are needed. For instance, methods for improving the potency of adoptively transferred cells and increasing the longevity of adoptively transferred cells would make adoptive cellular therapy a more attractive treatment modality.
The present invention addresses the need for improved methods and compositions for adoptive cellular therapy and provides other benefits associated with using an agonist of RORγ in medical therapy.